ClinVar Miner

Submissions for variant NM_001291303.3(FAT4):c.5792A>G (p.Tyr1931Cys)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091381 SCV001247399 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287232 SCV001473899 uncertain significance none provided 2020-02-03 criteria provided, single submitter clinical testing The FAT4 c.5792A>G; p.Tyr1931Cys variant (rs139716832) is reported in the literature in an individual affected with anencephaly, though it was not shown to be disease-causing (Ishida 2018). This variant is found in the non-Finnish European population with an overall allele frequency of 0.09% (114/127718 alleles) in the Genome Aggregation Database. The tyrosine at codon 1931 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Tyr1931Cys variant is uncertain at this time. References: Ishida M et al. A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly. Clin Genet. 2018;93(4):870–879.
Invitae RCV001091381 SCV001539214 uncertain significance not provided 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1931 of the FAT4 protein (p.Tyr1931Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs139716832, ExAC 0.08%). This variant has not been reported in the literature in individuals with FAT4-related conditions. ClinVar contains an entry for this variant (Variation ID: 871426). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001091381 SCV001743379 uncertain significance not provided no assertion criteria provided clinical testing

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